2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-13,14-didehydro-PGA, PGD, and PGE compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the C-1 carboxyl is replaced by a primary alcohol and the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 814,500, filed July 11, 1977, issued as U.S. Pat. No. 4,134,921 on Jan. 16, 1979; which application is a divisional application of Ser. No. 708,752, filed July 26, 1976, issued as U.S. Pat. No. 4,058,564 on Nov. 15, 1977.

The present invention relates to prostaglandin analogs for which the essential material constituting a disclosure therefor is incorporated by reference here from U.S. Pat. No. 4,058,564, issued Nov. 15, 1977. 

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein D is ##STR2## wherein R₈ is hydrogen or hydroxy; wherein M₁ is ##STR3## wherein R₅ is hydrogen or methyl; wherein L₁ is ##STR4## or a mixture of ##STR5## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro;wherein g is one, 2, or 3; and wherein m is one to 5, inclusive.
 2. A prostaglancin analog according to claim 1, wherein D is ##STR6##
 3. A prostaglandin analog according to claim 2, wherein R₈ is hydrogen.
 4. A prostaglandin analog according to claim 2, wherein R₈ is hydroxy.
 5. A prostaglandin analog according to claim 1, wherein D is ##STR7##
 6. A prostaglandin analog according to claim 1, wherein D is ##STR8##
 7. A prostaglandin analog according to claim 1, wherein D is ##STR9##
 8. A prostaglandin analog according to claim 7, wherein M₁ is ##STR10##
 9. 2-Decarboxy-2-hydroxymethyl-15-epi-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-11-deoxy-PGE₁, a prostaglandin analog according to claim
 8. 10. A prostaglandin analog according to claim 7, wherein M₁ is ##STR11##
 11. A prostaglandin analog according to claim 10, wherein m is
 3. 12. A prostaglandin analog according to claim 11, wherein g is
 3. 13. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-15-methyl-13,14-didehydro-11-deoxy-PGE₁, a prostaglandin analog according to claim
 12. 14. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-11-deoxy-PGE₁, a prostaglandin analog according to claim
 12. 15. A prostaglandin analog according to claim 11, wherein g is
 1. 16. A prostaglandin analog according to claim 15, wherein at least one of R₃ and R₄ is methyl.
 17. A prostaglandin analog according to claim 16, wherein R₃ and R₄ are both methyl.
 18. 2-Decarboxy-2-hydroxymethyl-16,16-dimethyl-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-11-deoxy-PGE₁, a prostaglandin analog according to claim
 17. 19. A prostaglandin analog according to claim 15, wherein at least one of R₃ and R₄ is fluoro.
 20. A prostaglandin analog according to claim 19, wherein R₃ and R₄ are both fluoro.
 21. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-16,16-difluoro-13,14-didehydro-11-deoxy-PGE₁, a prostaglandin analog according to claim
 20. 22. A prostaglandin analog according to claim 15, wherein R₃ and R₄ are both hydrogen.
 23. A prostaglandin analog according to claim 22, wherein R₅ is methyl.
 24. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-methyl-13,14-didehydro-11-deoxy-PGE₁, a prostaglandin analog according to claim
 23. 25. A prostaglandin analog according to claim 22, wherein R₅ is hydrogen.
 26. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-11-deoxy-PGE₁, a prostaglandin analog according to claim
 25. 27. A prostaglandin analog according to claim 1, wherein D is ##STR12##
 28. A prostaglandin analog according to claim 27, wherein M₁ is ##STR13##
 29. A prostaglandin analog according to claim 28, wherein m is
 3. 30. A prostaglandin analog according to claim 29, wherein g is
 3. 31. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-15-epi-15-methyl-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 30. 32. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-15-epi-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 30. 33. A prostaglandin analog according to claim 29, wherein g is
 1. 34. A prostaglandin analog according to claim 33, wherein at least one of R₃ and R₄ is methyl.
 35. 2-Decarboxy-2-hydroxymethyl-15-epi-3,7-inter-m-phenylene-4,5,6-trinor-16,16-dimethyl-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 34. 36. A prostaglandin analog according to claim 33, wherein at least one of R₃ and R₄ is fluoro.
 37. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-epi-16,16-difluoro-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 36. 38. A prostaglandin analog according to claim 33, wherein R₃ and R₄ are both hydrogen.
 39. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-epi-15-methyl-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 38. 40. A prostaglandin analog according to claim 27, wherein M₁ is ##STR14##
 41. A prostaglandin analog according to claim 40, wherein m is
 3. 42. A prostaglandin analog according to claim 41, wherein g is
 3. 43. A prostaglandin analog according to claim 42, wherein at least one of R₃ and R₄ is methyl.
 44. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-16,16-dimethyl-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 43. 45. A prostaglandin analog according to claim 42, wherein at least one of R₃ and R₄ is fluoro.
 46. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-16,16-difluoro-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 45. 47. A prostaglandin analog according to claim 42, wherein R₃ and R₄ are both hydrogen.
 48. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenulene-4,5,6-trinor-15-methyl-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 47. 49. A prostaglandin analog according to claim 41, wherein g is
 1. 50. A prostaglandin analog according to claim 49, wherein at least one of R₃ and R₄ is methyl.
 51. A prostaglandin analog according to claim 50, wherein only one or R₃ and R₄ is methyl.
 52. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-16-methyl-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 51. 53. A prostaglandin analog according to claim 50, wherin R₃ and R₄ are both methyl.
 54. 2-Decarboxy-2-hydroxymethyl3,7-inter-m-phenylene-4,5,6-trinor-16,16-dimethyl-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 53. 55. A prostaglandin analog according to claim 49, wherein at least one of R₃ and R₄ is fluoro.
 56. A prostaglandin analog according to claim 55, wherein R₃ and R₄ are both fluoro.
 57. A prostaglandin analog according to claim 56, wherein R₅ is methyl.
 58. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-methyl-16,16-difluoro-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 57. 59. A prostaglandin analog according to claim 56, wherein R₅ is hydrogen.
 60. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-16,16-difluoro-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 59. 61. A prostaglandin analog according to claim 49, wherein R₃ and R₄ are both hydrogen.
 62. A prostaglandin analog according to claim 61, wherein R₅ is methyl.
 63. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-methyl-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 62. 64. A prostaglandin analog according to claim 61, wherein R₅ is hydrogen.
 65. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-PGE₁, a prostaglandin analog according to claim
 64. 